Hysteresis and Allostery in Human UDP-Glucose Dehydrogenase Require a Flexible Protein Core
نویسندگان
چکیده
منابع مشابه
Structural Basis of Cooperativity in Human UDP-Glucose Dehydrogenase
BACKGROUND UDP-glucose dehydrogenase (UGDH) is the sole enzyme that catalyzes the conversion of UDP-glucose to UDP-glucuronic acid. The product is used in xenobiotic glucuronidation in hepatocytes and in the production of proteoglycans that are involved in promoting normal cellular growth and migration. Overproduction of proteoglycans has been implicated in the progression of certain epithelial...
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Elevated production of the matrix glycosaminoglycan hyaluronan is strongly implicated in epithelial tumor progression. Inhibition of synthesis of the hyaluronan precursor UDP-glucuronic acid (UDP-GlcUA) therefore presents an emerging target for cancer therapy. Human UDP-glucose 6-dehydrogenase (hUGDH) catalyzes, in two NAD(+)-dependent steps without release of intermediate aldehyde, the biosynt...
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UDP-glucose dehydrogenase catalyzes the NAD+-dependent 2-fold oxidation of UDP-glucose to give UDP-glucuronic acid. The putative aldehyde intermediate is not released from the active site and is presumably tightly bound. We have prepared UDP-7-deoxy-R-D-gluco-hept-6-ulopyranose, 5, that contains a methyl ketone at C-6 and cannot be further oxidized by the enzyme. Ketone 5 was found to be a comp...
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Eukaryotic protein kinases (EPKs) constitute a class of allosteric switches that mediate a myriad of signaling events. It has been postulated that EPKs' active and inactive states depend on the structural architecture of their hydrophobic cores, organized around two highly conserved spines: C-spine and R-spine. How the spines orchestrate the transition of the enzyme between catalytically uncomm...
متن کاملUDP-glucose dehydrogenase activity and optimal downstream cellular function require dynamic reorganization at the dimer-dimer subunit interfaces.
UDP-glucose dehydrogenase (UGDH) provides precursors for steroid elimination, hyaluronan production, and glycosaminoglycan synthesis. The wild-type UGDH enzyme purifies in a hexamer-dimer equilibrium and transiently undergoes dynamic motion that exposes the dimer-dimer interface during catalysis. In the current study we created and characterized point mutations that yielded exclusively dimeric ...
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ژورنال
عنوان ژورنال: Biochemistry
سال: 2018
ISSN: 0006-2960,1520-4995
DOI: 10.1021/acs.biochem.8b00497